Targeting DNA repeat sequences with Py-Im polyamides

Hairpin pyrrole-imdazole polyamides are cell-permeable, sequence-programmable oligomers that bind in the minor groove of DNA. This thesis describes studies of Py-Im polyamides targeted to biologically important DNA repeat sequences for the purpose of modulating disease states. Design of a hairpin polyamide that binds the CG dyad, a site of DNA methylation that can become dysregulated in cancer, is described. We report the synthesis of a DNA methylation antagonist, its sequence specificity and affinity informed by Bind-n-Seq and iteratively designed, which improves inhibitory activity in a cell-free assay by 1000-fold to low nanomolar IC50. Additionally, a hairpin polyamide targeted to the telomeric sequence is found to trigger a slow necrotic-type cell death with the release of inflammatory molecules in a model of B cell lymphoma. The effects of the polyamide are unique in this class of oligomers; its effects are characterized and a functional assay of phagocytosis by macrophages is described. Additionally, hairpin polyamides targeted to pathologically expanded CTG•CAG triplet repeat DNA sequences, the molecular cause of myotonic dystrophy type 1, are synthesized and assessed for toxicity. Lastly, ChIP-seq of Hypoxia-Inducible Factor is performed under hypoxia-induced conditions. The study results show that ChIP-seq can be employed to understand the genome-wide perturbation of Hypoxia-Inducible Factor occupancy by a Py-Im polyamide.

Absolute left-handed behaviors in a triangular elliptical-rod photonic crystal

In this paper we theoretically study the left-handed behaviors in a two-dimensional triangular photonic crystal made of elliptical rods in air. An absolute left-handed region is found in the second photonic band by using the plane wave expansion method to analyze the photonic band structure and equifrequency contours. Typical left-handed behaviors such as negative refraction, flat superlensing and plano-concave lensing are demonstrated by the finite-difference time-domain simulations. These behaviors are also compared with the quasi-negative refraction and the resulted focusing effects in a square-lattice two-dimensional photonic crystal. (c) 2005 Optical Society of America

Report upon the commercial fisheries in the Lancashire River Authority Area and their effect upon rod angling and spawning stock in the rivers and particularly the River Lune

The stock of salmon in any river is largely dependent upon the escapement of sufficient fish to ensure that an adequate quantity of ova is deposited and full use is made of all suitable spawning areas. At the present time, no accurate information is available on the numbers of fish entering rivers. Therefore, catch returns provide valuable information on fish stocks. This report summarises the catch returns for salmon in the Lancashire River Authority in the North of England for the years 1960-1964. Rivers included are the Lune, Ribble, Kent, Leven and Duddon.

An analysis of salmon rod catch data from castle fisheries, River Derwent, 1923-1989.

The aim of this study was to investigate the historical catch record from the Castle Fishery on the River Derwent over the period 1923 - 1989, to determine if changes had taken place in the composition of the catch and to examine the influence of flow on the performance of the fishery. The River Derwent is situated in West Cumbria, North West England. It flows from its source on Scafell Pike (NGR NY 229 089) westwards discharging into the Irish sea at Workington, a distance of 52 km. Over its length it receives water from an additional 214 km of stream, 5 large lakes and approximately 30 small tarns. The catchment drains a total area of 663 km2. The study concludes that through the time period there was considerable variation in catch between years. The trend was for the catch to increase steadily over the period 1923 - 1958, declining rapidly in 1959, after which catches increased steadily reaching a peak in the mid-sixties, before declining towards the end of the decade. During the seventies and eighties catches remained relatively stable at between 300 - 600 salmon per year until 1988 when over 2000 salmon were reported caught, the greatest number in any year over the study period.

Effectiveness of a Rigid Grate for Excluding Pacific Halibut, Hippoglossus stenolepis, From Groundfish Trawl Catches

A rigid grate was installed in a groundfish trawl to test its effectiveness in excluding Pacific halibut, Hippoglossus stenolepis, from commercial flatfish catches in the Gulf of Alaska. The grate was located ahead of the trawl codend to direct halibut toward an escape opening while allowing target species to pass through toward the codend. In an experimental fishery, the escape rate of halibut was estimated at 94%, while 72% of the Dover sole, Microstomas pacificus, 67% of the rex sole, Glyptocephalus zachirus, and 79% of the flathead sole, Hippoglossoides elassodon, were retained.